Katalin Susztak
Jan 1, 2006; 55:225-233
Complications

DE Kelley
May 1, 2000; 49:677-683
Articles

EJ Kurth-Kraczek
Aug 1, 1999; 48:1667-1671
Articles

Joseph G. Yu
Oct 1, 2002; 51:2968-2974
Obesity Studies

Michael P Stern
Apr 1, 1995; 44:369-374
Perspectives in Diabetes

Masayuki Saito
Jul 1, 2009; 58:1526-1531
Metabolism

Markus Tiedge
Nov 1, 1997; 46:1733-1742
Original Article

Joachim Spranger
Mar 1, 2003; 52:812-817
Pathophysiology

Franz M Matschinsky
Feb 1, 1996; 45:223-241
Banting Lecture 1995

G Perseghin
Aug 1, 1999; 48:1600-1606
Articles

R A DeFronzo
Dec 1, 1981; 30:1000-1007
Original Contribution

Charles M. Alexander
May 1, 2003; 52:1210-1214
Complications

Giulio Marchesini
Aug 1, 2001; 50:1844-1850
Pathophysiology

Tatsuya Hayashi
Aug 1, 1998; 47:1369-1373
Rapid Publications

C. Ronald Kahn
Aug 1, 1994; 43:1066-1085
Banting Lecture

T Inoguchi
Nov 1, 2000; 49:1939-1945
Articles

Eve Van Cauter
Mar 1, 1992; 41:368-377
Original Article

D A Pan
Jun 1, 1997; 46:983-988
Original Article

D Koya
Jun 1, 1998; 47:859-866
Articles

Samar I. Itani
Jul 1, 2002; 51:2005-2011
Rapid Publications

G Xu
Dec 1, 1999; 48:2270-2276
Articles

Andreas Festa
Apr 1, 2002; 51:1131-1137
Complications

David E. Cummings
Aug 1, 2001; 50:1714-1719
Rapid Publications

Norikazu Maeda
Sep 1, 2001; 50:2094-2099
Pathophysiology

Thomas A. Buchanan
Sep 1, 2002; 51:2796-2803
Pathophysiology

ME Griffin
Jun 1, 1999; 48:1270-1274
Articles

U.K. Prospective Diabetes Study Group
Nov 1, 1995; 44:1249-1258
Perspectives in Diabetes

Steven E Kahn
Nov 1, 1993; 42:1663-1672
Original Article

JC Henquin
Nov 1, 2000; 49:1751-1760
Articles

HE Hohmeier
Mar 1, 2000; 49:424-430
Articles

National Diabetes Data Group
Dec 1, 1979; 28:1039-1057
Articles

Alexandra E. Butler
Jan 1, 2003; 52:102-110
Islet Studies

Gerald M Reaven
Dec 1, 1988; 37:1595-1607
Banting Lecture 1988

Night shift work, behavioral rhythms, and the common MTNR1B risk single nucleotide polymorphism (SNP), rs10830963, associate with type 2 diabetes; however, whether they exert joint effects to exacerbate type 2 diabetes risk is unknown. Among employed participants of European ancestry in the UK Biobank (N = 189,488), we aimed to test the cross-sectional independent associations and joint interaction effects of these risk factors on odds of type 2 diabetes (n = 5,042 cases) and HbA_1c levels (n = 175,156). Current shift work, definite morning or evening preference, and MTNR1B rs10830963 risk allele associated with type 2 diabetes and HbA_1c levels. The effect of rs10830963 was not modified by shift work schedules. While marginal evidence of interaction between self-reported morningness-eveningness preference and rs10830963 on risk of type 2 diabetes was seen, this interaction did not persist when analysis was expanded to include all participants regardless of employment status and when accelerometer-derived sleep midpoint was used as an objective measure of morningness-eveningness preference. Our findings suggest that MTNR1B risk allele carriers who carry out shift work or have more extreme morningness-eveningness preference may not have enhanced risk of type 2 diabetes.

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ~26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P < 6.94 x 10^–8). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1. Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy.

Permanent neonatal diabetes mellitus (PNDM) is caused by reduced β-cell number or impaired β-cell function. Understanding of the genetic basis of this disorder highlights fundamental β-cell mechanisms. We performed trio genome sequencing for 44 patients with PNDM and their unaffected parents to identify causative de novo variants. Replication studies were performed in 188 patients diagnosed with diabetes before 2 years of age without a genetic diagnosis. EIF2B1 (encoding the eIF2B complex α subunit) was the only gene with novel de novo variants (all missense) in at least three patients. Replication studies identified two further patients with de novo EIF2B1 variants. In addition to having diabetes, four of five patients had hepatitis-like episodes in childhood. The EIF2B1 de novo mutations were found to map to the same protein surface. We propose that these variants render the eIF2B complex insensitive to eIF2 phosphorylation, which occurs under stress conditions and triggers expression of stress response genes. Failure of eIF2B to sense eIF2 phosphorylation likely leads to unregulated unfolded protein response and cell death. Our results establish de novo EIF2B1 mutations as a novel cause of permanent diabetes and liver dysfunction. These findings confirm the importance of cell stress regulation for β-cells and highlight EIF2B1’s fundamental role within this pathway.

Long-term hyperglycemia in patients with diabetes leads to human serum albumin (HSA) glycation, which may impair HSA function as a transport protein and affect the therapeutic efficacy of anticoagulants in patients with diabetes. In this study, a novel mass spectrometry approach was developed to reveal the differences in the profiles of HSA glycation sites between patients with diabetes and healthy subjects. K199 was the glycation site most significantly changed in patients with diabetes, contributing to different interactions of glycated HSA and normal HSA with two types of anticoagulant drugs, heparin and warfarin. An in vitro experiment showed that the binding affinity to warfarin became stronger when HSA was glycated, while HSA binding to heparin was not significantly influenced by glycation. A pharmacokinetic study showed a decreased level of free warfarin in the plasma of diabetic rats. A preliminary retrospective clinical study also revealed that there was a statistically significant difference in the anticoagulant efficacy between patients with diabetes and patients without diabetes who had been treated with warfarin. Our work suggests that larger studies are needed to provide additional specific guidance for patients with diabetes when they are administered anticoagulant drugs or drugs for treating other chronic diseases.

Western Bureau: Some displaced Iberostar employees in Rose Hall, St James, are angry with their employer, charging that they have been unable to benefit from the Government’s COVID-19 relief programme because of the hotel’s failure to pay over...

Sandra Ferguson resides with her children and grandchildren in a concrete dwelling that is sectioned into four living quarters in the Fort George Road area of Annotto Bay. With 10 of them sharing kitchen and bathroom facilities, Ferguson said...

Days after The Gleaner reported a clarion call from Port Maria Mayor Richard Creary for the quarantine of St Mary communities owing to growing concerns about the spread of COVID-19 in the parish, the Government responded with the lockdown of three...

It was a double whammy of inconvenience for Sharon Carter, a vendor in Metcalfe Market, Annotto Bay. Carter, who lives in St Catherine, had just recently been relieved of the lockdown in the parish and is now being affected by the quarantine which...

No sooner than the Government’s announced its intention to restart the economy, private sector groups are advocating for longer working hours to fast-track recovery during the COVID-19 pandemic. In a collaborative move, the Jamaica Manufacturers...

May 10, Mother’s Day, is a special day on the calendar when many people make big plans to spend the day or the weekend with their mothers. However, this year some people may rethink their plans as they would not want to expose their beloved mothers...

BRIDGETOWN, Barbados, CMC – The Barbados-based the Caribbean Disaster Emergency Management Agency (CDEMA) says its executive director, Ronald Jackson, is leaving the post after seven years “of unwavering and exemplary service to the...

KINGSTOWN, St Vincent, CMC – The St Vincent and the Grenadines Government has denied a United States-based airline permission to land, dashing hopes that an estimated 300 nationals employed with a US-based cruise line would have arrived home...

PORT AU PRINCE, Haiti, CMC – The Ministry of Public Health has confirmed that a 20-year-old man has become the seventh person in Haiti to die of the coronavirus (COVID-19). It is urging the population to follow restriction measures, including...

HAMILTON, Bermuda, CMC –  Bermuda recorded its seventh COVID-19 death on Saturday as Finance Minister Curtis Dickinson announced that he would need to rewrite this year’s budget because of the battering from the global...

BRIDGETOWN, Barbados, CMC – A few weeks before the official start of the 2020 Atlantic Hurricane Season, forecasters at the US-based Colorado State University are warning that the six-month period will be more active than normal. The CSU...

As of May 6, officials in Nevis are reporting that there are no active cases of the deadly COVID-19 virus on the island. This was confirmed Tuesday by Premier Mark Brantley, Minister responsible for Health, in the Nevis Island Administration....

PORT OF SPAIN, Trinidad, CMC – The Trinidad-based Caribbean Public Health Agency (CARPHA) is urging people in the region to remember that despite the coronavirus (COVID-19) pandemic, they must be mindful that other public health threats still...